DRESS syndrome

Definition

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also called drug-induced hypersensitivity syndrome (DIHS), is a severe, delayed-onset type IV (T cell-mediated) drug reaction. It is characterised by rash, fever, marked eosinophilia and involvement of internal organs. Together with Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalised exanthematous pustulosis (AGEP), it is one of the severe cutaneous adverse drug reactions.

Aetiopathogenesis

• Typical triggers: frequently caused by antiepileptic drugs (including carbamazepine, phenytoin, lamotrigine), a uricostatic drug and sulfonamides; some anti-infectives are also implicated.
• Genetic predisposition: certain HLA alleles increase the risk, e.g. HLA-B*58:01 with exposure to a uricostatic drug, HLA-B*15:02 with carbamazepine (mainly in people of Asian ancestry) and HLA-B*13:01 with dapsone (in people of Chinese ancestry).
• Mechanism: T cell-mediated delayed hypersensitivity (type IV).

Clinical features

• Latency: typically 2 to 6 weeks after first intake; onset up to 12 weeks after starting the drug or after an increase in the amount is possible.
• Skin and general symptoms: fever, widespread rash, facial edema, generalised edema and lymphadenopathy.
• Organ involvement: hepatitis, pneumonitis and myocarditis; the kidneys may also be involved.
• Course: symptoms may persist or recur for several weeks after exposure has ended; thyroiditis has been described as a late sequela.

Diagnosis

• History: all drugs started in the preceding weeks, as the reaction appears only after days to weeks; not only the most recently started drug is suspect.
• Full blood count: marked eosinophilia and atypical lymphocytes.
• Organ assessment: liver tests, renal function and urinalysis; if myocarditis or pneumonitis is suspected, further cardiac and pulmonary investigations.
• Skin biopsy: often suggestive but not diagnostic on its own.
• Provocation tests: fundamentally excluded after DRESS syndrome.
• HLA typing: can indicate risk for specific substances in certain populations.

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Further reading (open access)

1. MSD Manual Professional: Drug Hypersensitivity
2. MSD Manual Professional: Drug Eruptions and Reactions
3. MSD Manual Professional: Overview of Allergic and Atopic Disorders
4. Europe PMC (J Clin Med 2023): Renal Manifestations of DRESS Syndrome – Systematic Review of 71 Cases

Cross-references